The project consists of a series of clinical trials evaluating the clinical efficacy and safety of experimental therapeutic agents for the control of acute pain and perioperative apprehension in ambulatory patients undergoing minor surgical procedures. The surgical removal of impacted third molars serves as a model for minor surgical procedures with associated intraoperative and postoperative pain and perioperative apprehension. All studies are double-blind with randomly allocated, parallel treatment groups and multiple dependent measures of therapeutic efficacy and clinical safety. Spiradoline, a novel analgesic which acts at the kappa opioid receptor, was evaluated in 75 oral surgery patients in comparison to 10 mg of IM morphine and placebo. Data from subjects who received the IM injection in the gluteus did not show any activity for spiradoline and only minimal activity of morphine. Preliminary results for IM injection in the deltoid suggest that spiradoline at 4.8 micrograms per kilogram is equipotent with 10 mg of morphine but that its duration of activity is only 30-60 minutes. The sample size is being increased to 100 subjects to allow collection of sufficient data following deltoid administration to support these preliminary findings. A second study is evaluating the analgesic efficacy of two antihistamine drugs in comparison to ibuprofen and placebo. Terfenadine, a HI histamine receptor blocker, and ranitidine, a H2 histamine receptor blocker are administered one hour prior to oral surgery and the onset and severity of postoperative pain monitored for four hours postoperatively. A demonstration of analgesic activity for either antihistamine will provide a rationale for a factorial study comparing ibuprofen alone, an antihistamine alone, and the combination of an antihistamine and ibuprofen, to placebo. Drugs acting through separate mechanisms should result in additive analgesia and the lack of central effects for these two drug classes should provide a therapeutic advantage without increased side effects in ambulatory patients. A parallel series of investigations are evaluating the safety and efficacy of drugs used for anxiety relief in patients undergoing minor surgical procedures with local anesthesia. A dose-range study of the combination of oral triazolam, a benzodiazepine, and nitrous oxide indicated that 0.25 mg of triazolam in combination with nitrous oxide resulted in therapeutic benefit.